Nicergoline in dementia: A review of its pharmacological properties and therapeutic potential

Nicergoline is a semisynthetic ergoline derivative indicated for the treatment of cognitive impairment in various forms of dementia. It is currently available for use in Italy and some other European countries, in Latin America and the Near and Far East. In animal studies nicergoline exhibits a broad spectrum of actions on cellular and molecular mechanisms involved in the pathophysiology of dementia. Nicergoline appears to enhance cholinergic and catecholaminergic neurotransmitter function and improve related cognitive deficits; stimulate phosphoinositide turnover; modulate protein kinase C (PKC) translocation and PKC- mediated alpha-secretase processing of amyloid precursor protein; increase regional cerebral blood flow, and glucose uptake and utilisation; activate protein synthesis; protect neurons from death induced by oxidative stress or apoptosis; and interact with endogenous nerve growth factor-mediated processes providing trophic support to cholinergic neurons. Whether these actions are interrelated or represent multiple, unrelated effects is still unknown, but all may be relevant to the therapeutical use of the drug. Recent double-blind, placebo-controlled, randomised clinical studies of up to 12 months duration indicated a measurable effect of nicergoline on cognitive performance in patients with dementing illnesses. Medium and long term treatment resulted in significantly greater cognitive improvement or less decline than placebo as measured by Mini-Mental State Examination (MMSE) or Alzheimers Disease Assessment Scale - Cognitive Subscale (ADAS- cog) scores. While deterioration represents the natural course of the disease, nicergoline-treated patients improved or maintained their previous clinical status. The objective improvement of the cognitive symptoms was paralleled by a stabilised or improved clinical global condition as evaluated by clinicians, caregivers and patients. Nicergoline was well tolerated in all clinical studies. The type, frequency and severity of adverse events were generally comparable with those observed in the placebo control groups. No clinically or statistically significant changes in vital signs and laboratory evaluations were reported, except for an asymptomatic increase of serum uric acid levels. Overall, data strongly support the hypothesis that nicergoline might interfere with fundamental molecular mechanisms underlying cognitive processes in vivo. The clinical results also indicate that nicergoline is a well tolera